The development of ultra-fast, ultra-short pulsed lasers as surgical tools for ophthalmic surgery has led to a need for enhanced diagnostic capabilities. For example, recent advances in optical surgery techniques include the use of femto-second (fs) lasers for intrastromal and non-invasive refractive surgery. For many of these techniques, high resolution optical imaging is required to thoroughly evaluate the precision, efficiency and effectiveness of these fs surgical lasers. In addition to its use with surgical procedures, it is known that high resolution optical imaging may also be used as a diagnostic tool. In particular, high resolution optical imagining may be useful in some instances to evaluate the health of various parts of the eye, such as the fundus. For instance, it is known that by imaging and studying layers of the fundus, it is possible to detect the early onset of many optical maladies such as age related macular degeneration and glaucomateous disease.
The anatomy of the fundus of an eye is known to comprise several distinct layers, to include axons, ganglion cells, bipolar cells, photoreceptors (rods and cones), pigment cells and the choroid. Further, it is well known that healthy photoreceptors within the fundus of the eye are all aligned substantially parallel to each other. Also, healthy photoreceptors are separated from each other through a distance of about two microns by regions of matrix material. On the other hand, misshapen and misaligned receptors, that are not substantially parallel to each other, are indicative of an unhealthy fundus and, thus, a potential problem. In addition to the photoreceptors, the health of other layers of the fundus can be evaluated. For example, the Henle-fibers are the axons of the bi-polar cells, connecting the photoreceptor signal to the brain. In a healthy Henle-fiber layer, the Henle-fibers have a very specific directional orientation. On the other hand, distortions in the Henle-fiber layer and the orientations of the fibers may be an early indication of age related macular degeneration.
It is important to note that much of the tissue in the fundus of an eye is substantially asymmetrical or anisotropic in nature. Of particular interest here is that the transverse structural properties of the fundus tissue are different from its longitudinal structural properties. In large part this difference is due to the presence of collagen and nerve fibers in the fundus tissue. Importantly, the asymmetrical, anisotropic nature of the fundus tissue offers the possibility that the fundus can effectively respond to Second Harmonic Generation (“SHG”) imaging.
As a general proposition, SHG imaging is due to the second order, non-linear, polarization of light as it is radiated from an illuminated sample. For instance, during SHG it happens that red photons are converted into blue photons by a phenomenon which is commonly referred to as “photon conversion”. Specifically, it happens that two incident red photons (with wavelengths λ on the order of 880 nm) are converted to a single, radiated blue photon (with a wavelength of λ/2 or 440 nm). The SHG response or return light that is so generated, with a wavelength of 440 nm, can be used to create an image of the illuminated tissue.
Importantly, the SHG response induced by the illumination of anisotropic tissue in the fundus is non-linear. Due to this non-linearity, the SHG response will increase with the square of the power density of the incident laser beam. It should be noted here that the power density of the incident laser beam is a function of both the input energy and the volume of the focal point. It follows, therefore, that the power density of the incident laser beam can be increased if the illuminated volume, or more specifically the Point Spread Function (“PSF”) of the laser beam focal point, can be reduced. In this context, the PSF is a three dimensional volumetric measurement that defines the finest volume of focus for a particular light beam. For many presently used laser systems, the PSF is generally on the order of 6 μm×6 μm×200 μm. With adaptive optics, however, it is possible to reduce the PSF to about 2 μm×2 μm×20 μm. This represents a reduction in volume by a factor of about 100. Accordingly, when the PSF is reduced by a factor of about 100, there is a corresponding increase in the power density, also by a factor of about 100. Adaptive optics, such as those disclosed in U.S. Pat. No. 6,220,707, entitled “Method for Programming an Active Mirror to Mimic a Wavefront” issued to J. Bille, offer the potential to effectively focus the incident beam to a smaller PSF, while maintaining a substantially aberration-free beam of light.
Due to its anisotropic nature, the fundus of the eye is well suited for SHG imaging. Specifically, various layers of the fundus tissue, to include the photoreceptors, the nerve fiber layer and the Henle-fibers, contain anisotropic tissue. Further, the anisotropic tissues are surrounded by a substantially isotropic matrix. Consequently, the anisotropic tissues will produce a SHG response when illuminated, while the surrounding isotropic materials will produce no such response. An important additional consideration is that the geometry of the various fundus layers is compatible with the smaller PSF desired for SHG imaging. Specifically, the distance between anisotropic elements in the various layers of the fundus, such as the distance between healthy photoreceptors, is on the order of 2 μm. Also, the depth of the various layers is generally equal to or greater than 20 μm. It is therefore possible, with a PSF of 2 μm×2 μm×20 μm, to detect a single element, such as a photoreceptor, within a single layer of the fundus, and to determine its location in the fundus relative to other elements.
In light of the above, it is an object of the present invention to provide a system for imaging the fundus of the human eye. Another object of the present invention is to provide a system which can resolve the various individual tissue layers of the fundus, particularly the photoreceptor layer, for diagnostically evaluating the health of the various fundus tissues. Still another object of the present invention is to provide a system for imaging the fundus of the human eye that produces a Second Harmonic Generation image. Yet another object of the present invention is to provide a system for imaging the fundus of the human eye that is easy to use, relatively simple to manufacture and comparatively cost effective.